Accelerated Mining of Extremophile Natural Products: An Integrated Omics Approach Captures Antiviral Lipopeptides

Using a combined culturomics-driven activation and metabologenomics approach, a new family of lipopeptides, nocardins A-E (1-5, respectively), were identified and isolated from Arctic-derived Nocardia sp. L016. Their planar structures and absolute configurations were determined through comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and Marfey's analysis. Biosynthetically, nocardins are assembled by a previously uncharacterized NRPS gene cluster (ncd). Notably, 1 and 2 demonstrated significant anti-influenza activity against the PR8 virus, exhibiting potency 2-4-fold higher than that of positive control ribavirin. This integrated omics strategy provides an effective route for accelerating the discovery of new structurally unique natural products from extremophiles.